The proposed research deals with several aspects of the central modulation of somatosensation. One of the main goals is to identify the neurotransmitter of cortical neurons at the origin of the descending pathways to the somatosensory thalamus, the dorsal column nuclei and the spinal cord in rats. Available evidence suggests that glutamate may be involved in these neurons and we will employ an immunocytochemical approach combined with the retrograde transport of dyes to verify this. Double-labeling immunocytochemistry will be also employed to investigate whether some of the peptides known to be present in non-pyramidal cortical neurons co-localize with glutamergic neurons in layer VI. We also wish to investigate whether modulation of VB activity in cats by the cortex and other subcortical centers (e.g. raphe nuclei, periaqueductal gray, etc.) is primarily mediated via direct contacts upon intrinsic GABA - ergic neurons. Combination of immunocytochemistry against glutamic acid decarboxylase (GAD) and anterograde tracing techniques will be employed at the electron microscopical level. This part of the planned research will elucidate mechanisms presumably involved in some basic thalamic functions and will establish a solid basis for further insights in how input from different centers may affect the activity of VB neurons. As a third main goal, we'll try to answer whether GAD positive neurons in cat's VB contain peptides that are believed to be involved in some form of control of neurotransmission. The rationale for this part of the research lies mainly in the demonstration that GABA - ergic neurons, e.g. in the cortex, may express other molecular markers. Furthermore species differences in the presence of GABA - ergic neurons and co-localisation of other markers may reflect increasing elaboration and complexity of functional features of thalamic nuclei.